Man-made antibodies show promise in attacking cancer cells in animal models

April 16, 2018, Duke University Medical Center
Micrograph showing prostatic acinar adenocarcinoma (the most common form of prostate cancer) Credit: Wikipedia

Using chemotherapy along with aptamers—lab-made molecules that function like antibodies—Duke Health researchers showed that they can zero in on and kill prostate cancer tumors in mice while leaving healthy tissue unscathed.

The finding suggests that aptamers could form the basis of new cancer therapies if additional studies in animals and humans bear out.

"The benefit of aptamers compared to is that we have more control over where they go and what they do," said senior author Bruce Sullenger, Ph.D., professor in the departments of Surgery and Pharmacology and Cancer Biology at Duke. "In our study, we also developed an antidote that shuts down the almost immediately, and this is an advantage if, for whatever reason, there might be an adverse reaction."

Sullenger and colleagues—including lead author Bethany Powell Gray, Ph.D., and co-author Linsley Kelly, Ph.D.—published their findings online during the week of April 16 in the journal Proceedings of the National Academy of Sciences.

Man-made aptamers can be created to target cancer cells, much like the body's naturally generated antibodies home in on pathogens such as viruses or bacteria. Recent drug advances have used antibodies in conjunction with chemotherapy to create immunotherapies that successfully fight cancer.

But inflammation and other side effects are common in these drug combinations, because it's difficult to control where and how strongly the antibodies trigger immune responses outside of the cancer cells.

"A need exists for new tumor-targeting therapies that are easier to manipulate and synthesize," Kelly said.

Aptamers are increasingly being studied as good alternatives. They are created using single RNA or DNA strands, which have the same targeting potential as antibodies, but appear to be nontoxic.

In their study on cancer cells, the Duke team focused on an RNA ligand called E3, which selectively targets . They combined the E3 aptamer with a small dose of a highly toxic chemotherapy agent. Then they injected the aptamer/drug combination in mice that harbor human prostate cancer tumors.

Mice with prostate cancer tumors receiving the investigational treatment lived up to 74 days, compared to 46 days for mice that did not receive the treatment.

Additionally, the researchers developed an antidote to block toxicity from the E3 aptamer-drug conjugate, providing a safety switch in the unexpected event of normal cells being killed.

"That was one of the really exciting things from this work," Powell Gray said. "Because they are single strands of RNA, they can be reversed by using a complimentary portion of RNA that will bind and make a double strand to unfold the aptamer."

The researchers said studies will continue in animals and be tested in other types of .

"This study demonstrates that E3 RNA selectively internalizes into cellsand that E3-highly toxic drug conjugates are potent anti-tumor agents, representing a potential new therapeutic approach," Sullenger said.

Explore further: Researchers develop a new generation of tumor-specific aptamer-drug conjugate

More information: Bethany Powell Gray el al., "Tunable cytotoxic aptamer–drug conjugates for the treatment of prostate cancer," PNAS (2018). www.pnas.org/cgi/doi/10.1073/pnas.1717705115

Related Stories

Researchers develop a new generation of tumor-specific aptamer-drug conjugate

December 15, 2017
The toxic nature of chemotherapy poses a great challenge to clinical treatment of cancer. A team of scholars from the School of Chinese Medicine (SCM) of Hong Kong Baptist University (HKBU) devoted their efforts to the development ...

Potential cholesterol-lowering drug molecule has prostate cancer fighting capabilities

April 14, 2016
Standard treatment for prostate cancer can include chemotherapy that targets receptors on cancer cells. However, drug-resistant cancer cells can emerge during chemotherapy, limiting its effectiveness as a cancer-fighting ...

Recommended for you

Some brain tumors may respond to immunotherapy, new study suggests

December 10, 2018
Immunotherapy has proved effective in treating a number of cancers, but brain tumors have remained stubbornly resistant. Now, a new study suggests that a slow-growing brain tumor arising in patients affected by neurofibromatosis ...

Study finds higher risk of breast cancer for women after giving birth

December 10, 2018
Younger women who have recently had a child may have a higher risk of breast cancer than their peers of the same age who do not have children, according to a large-scale analysis co-led by a University of North Carolina Lineberger ...

A code for reprogramming immune sentinels

December 10, 2018
For the first time, a research team at Lund University in Sweden has successfully reprogrammed mouse and human skin cells into immune cells called dendritic cells. The process is quick and effective, representing a pioneering ...

Researchers develop personalized medicine tool for inherited colorectal cancer syndrome

December 10, 2018
An international team of researchers led by Huntsman Cancer Institute (HCI) at the University of Utah (U of U) has developed, calibrated, and validated a novel tool for identifying the genetic changes in Lynch syndrome genes ...

Study shows key enzyme linked to therapy resistance in deadly lung cancer

December 10, 2018
Researchers at The University of Texas MD Anderson Cancer Center have identified a link between an enzyme tied to cancer formation and therapy resistance in patients with epidermal growth factor receptor (EGFR)-mutant non-small ...

Potential seen for tailoring treatment for acute myeloid leukemia

December 8, 2018
Advances in rapid screening of leukemia cells for drug susceptibility and resistance are bringing scientists closer to patient-tailored treatment for acute myeloid leukemia (AML).

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.